PKA-RIIβ autophosphorylation modulates PKA activity and seizure phenotypes in mice
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چکیده
منابع مشابه
Single Turnover Autophosphorylation Cycle of the PKA RIIβ Holoenzyme
To provide tight spatiotemporal signaling control, the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) holoenzyme typically nucleates a macromolecular complex or a "PKA signalosome." Using the RIIβ holoenzyme as a prototype, we show how autophosphorylation/dephosphorylation of the RIIβ subunit, as well as cAMP and metal ions, contribute to the dynamics of PKA signaling. Whi...
متن کاملStructure and allostery of the PKA RIIβ tetrameric holoenzyme.
In its physiological state, cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) is a tetramer that contains a regulatory (R) subunit dimer and two catalytic (C) subunits. We describe here the 2.3 angstrom structure of full-length tetrameric RIIβ(2):C(2) holoenzyme. This structure showing a dimer of dimers provides a mechanistic understanding of allosteric activation by cAMP. Th...
متن کاملcAMP-dependent PKA Signaling Induces TNFR1 Exosome-like Vesicle Release via Anchoring of PKA Regulatory Subunit RIIβ to BIG2
The 55-kDa, type I tumor necrosis factor receptor (TNFR1) can be released to the extracellular space by two mechanisms, the proteolytic cleavage and shedding of soluble receptor ectodomains and the release of full-length receptors within exosome-like vesicles. We have shown that the brefeldin A-inhibited guanine nucleotide-exchange protein BIG2 associates with TNFR1 and selectively modulates th...
متن کامل1 Phosphorylation of the PKA regulatory subunit modulates PKA - AKAP interaction , substrate phosphorylation and calcium signaling in cardiac cells
Subcellular compartmentalization of protein kinase A (PKA) by A-kinase anchoring proteins (AKAPs) facilitates local protein phosphorylation. However, little is known about how PKA targeting to AKAPs is regulated in the intact cell. PKA binds to an amphipathic helical region of AKAPs via an Nterminal domain of the regulatory subunit. In vitro studies showed that autophosphorylation of type II re...
متن کاملPKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis.
Stimulus-secretion coupling is an essential process in secretory cells in which regulated exocytosis occurs, including neuronal, neuroendocrine, endocrine, and exocrine cells. While an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) is the principal signal, other intracellular signals also are important in regulated exocytosis. In particular, the cAMP signaling system is well known...
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ژورنال
عنوان ژورنال: Communications Biology
سال: 2021
ISSN: 2399-3642
DOI: 10.1038/s42003-021-01748-4